Based on the demand or the desire of medical-diagnostic applications for displaying an anatomically correct overall image of the eye, different approaches are proposed in this connection in the known prior art.
In particular, the attempt was made to implement such displays by means of magnetic resonance imaging (MRI) and computed tomography (CT). The MRI has the disadvantage here that the resolution depends on the implementable magnetic field strength which, in turn, is mainly limited by the needed measuring volume. The resolution of the MRI, which lies in the mm-range, is in general not sufficient for high-precision diagnostic examinations on humans. CT, in turn, has the disadvantages of exposure to radiation and the need of costly equipment. Moreover, the contrasts for X-rays do not always correlate with the optically relevant variables in the visible wavelength range (such as refractive index transitions or scattering), which can be a problem in ophthalmology.
In contrast to that, better results can be achieved in the different eye regions by using optical measurement methods that are adapted to the respective eye regions. In the anterior region, these methods are, for example, the optical coherence tomography (anterior chamber OCT, AC-OCT) as well as slit lamp imaging and Scheimpflug imaging; in the posterior eye region, however, these methods are retinal optical coherence tomography and also confocal scanning and fundus imaging.
However, in the following, such approaches are addressed in which displaying the whole eye is based on at least one coherence tomography measurement which extends over the entire length of the eye.
The methods and measurement devices based on optical coherence tomography (OCT) are in the known prior art the most widely accepted solutions for tomographic imaging of eye structures.
In OCT methods, coherent light is used with the aid of an interferometer for distance measurement and imaging on reflective and scattering samples. During a scan into the depth on the human eye, due to changes of the refractive index occurring on optical boundary surfaces and due to volume scattering, the OCT methods deliver measurable signals. The optical coherence tomography is a very sensitive and fast method for interferometric imaging which has found broad acceptance in particular in the medical field and in basic research. OCT images (OCT scans) of eye structures are frequently used in ophthalmology for diagnosis and therapy monitoring, and also for planning of surgical interventions and for selecting implants.
The basic principle of the OCT method, as described, for example, in U.S. Pat. No. 5,321,501, is based on white-light interferometry and compares the transit time of a signal with the aid of an interferometer (primarily a Michelson interferometer). Here, the arm having a known optical path length (=reference arm) is used as a reference for the measuring arm in which the sample is located. The interference of the signals from both arms forms a pattern from which the scattering amplitudes can be determined in dependence on the optical delay between the arms, and thus a depth-dependent scattering profile can be determined which, analogous to ultrasonic technology, is designated as A-scan. In multi-dimensional raster methods, the beam is then guided transversally in one or two directions, as a result of which a two-dimensional B-scan or a three-dimensional volume tomogram can be recorded. Here, the amplitude values of the individual A-scans are represented in linear or logarithmized grey scale values or false color values. The technology of recording individual A-scans is also designated as optical coherence domain reflectometry (OCDR); in contrast to this, OCT implements two- or three-dimensional imaging through lateral scanning.
From the OCT methods used in ophthalmology, two different basic types have established themselves. For determining the measured values with the first type, the length of the reference arm is changed and the intensity of the interference is continuously measured without considering the spectrum. This method is designated as “time domain” method (U.S. Pat. No. 5,321,501 A). On the contrary, in the other method, the method designated as “frequency domain”, the spectrum is considered when determining the measured values, and the interference of the individual spectral components is recorded.
Thus, on the one hand, this is referred to as signal in the time domain and, on the other, as signal in the frequency domain. The advantage of the “frequency domain” method is the simple and fast simultaneous measurement, wherein complete information about the depth can be determined without the need of movable parts. This increases stability and speed (U.S. Pat. No. 7,330,270 B2), as a result of which in particular three-dimensional OCT images have been made possible.
Furthermore, in the frequency domain OCT, a distinction is made whether the spectral information is obtained by means of a spectrometer (“spectral domain OCT”, SD-OCT) or by means of spectral tuning of the light source (“swept source OCT”, SS-OCT).
A great technological advantage of OCT is the decoupling of the depth resolution from the transversal resolution. Through this it is possible in particular in the case of limited numerical apertures to achieve a very good axial resolution, for example, so as to be able, despite aperture limitation by the pupil, to examine retina layers in the axial direction with high (<20 μm) and highest (<4 μm) resolutions. The contactless OCT measurement based on backscattering and reflection thus enables generating microscopic images in vivo. A further advantage is the efficient suppression of non-coherent portions of disturbing light. “Axial direction” means here the direction of the depth profile displayed in the A-scan. Due to local refractions, said direction can also vary in A-scan portions but is usually nearly parallel to the optical axis or to the visual axis from the cornea vertex to the fovea of an eye to be examined.
A first use of the display of the overall depth profile of the backscattering of the eye, which display is based on coherence reflectometry measurements (OCDR), is described by F. Lexer et al. in [1]. Here it is emphasized again that the exact knowledge of the intraocular distances is an important resource of modern ophthalmology, for example for matching intraocular lens implants. While the axial eye length and the depth of the anterior chamber are absolutely necessary for precise calculations of the refraction power of intraocular lenses for cataract surgeries, the accurate measurement of the corneal thickness is important for refractive surgery. For diagnosing various diseases and for monitoring the therapeutic effects, the determination of the thickness of the retinal layers can be helpful. The approach described in [1] is based on a SS-FD-OCDR system of medium quality and it allows measuring the distances of all optical surfaces in the eye over the entire length of the eye. While it was possible to achieve a good resolution with this approach when scanning the entire measuring range of model eyes, this was no longer possible for the simultaneous “in vivo” measurement of three intraocular distances. It has been found that the approach for measuring intraocular distances with an accuracy up to at best 30 μm achieves a sufficient resolution; however, for high-resolution OCDR or OCT applications, this approach is no longer suitable.
In the published applications US 2007/216909 A1, US 2007/291277 A1 and US 2008/100612 A1, SD-OCT systems are described which comprise a switchable focus and/or a switchable reference plane (zero-delay) of the OCT arrangement. Here, during a retinal scan, the focus should lie in the region of the retina, and during a corneal scan, the focus should lie in the region of the cornea. In this manner, an OCT scan with high lateral resolution of the anterior or posterior portion of the eye is possible. Furthermore, it is described that a retinal scan with the rotation point of the scan being in the iris/pupil plane is advantageous. With the solutions proposed here, two-dimensional scans with high resolution as well as three-dimensional scans (data cubes) can be recorded and evaluated.
The object to be achieved here was to make OCT scans possible in each case with high resolution and high signal strength of the anterior and also the posterior portions of the eye and with only one device. No proposal for a solution for the implementation of whole-eye scans or for the combination of retinal and corneal scans so as to form a single image of the eye was disclosed.
Another “frequency domain”-based OCT system is described by Walsh et al. in WO 2010/009447 A2. The spectral information is obtained either by means of a spectrometer (SD-OCT) or by means of a spectrally tunable light source (swept source, SS-OCT). Hereby, the eye can be displayed in a plurality of portions along the optical axis or also completely by means of A-, B-, or C-scans. The solution describes a method for a whole-eye scan and also for consecutive partial scans. Here too, the scan rotation point in the pupil needed for a retinal scan is emphasized. Furthermore, many possible opthalmological applications of whole-eye scan are described.
Furthermore, WO 2010/009447 A2 describes the apparently practicable combination of a plurality of OCT scans by means of fast whole-eye scout scans or “via stitched” scans via mathematical AND or OR operators.
However, WO 2010/009447 A2 does not describe the different types of displays in the scan data resulting from the scan modalities, and no solution for a necessary registration of the data to one another is described. However, an AND or OR conjunction can only be applied after a sufficient registration of the scan to one another other has been performed. A registration is to be understood as an allocation of corresponding structures which are included in different scans, and also, based on said allocation, as a spatial alignment and matching of scans with each other, in particular for an easier visualization, analysis and motion correction (U.S. Pat. No. 7,365,856 B2).
The solution described in WO 2012/009447 A2 is therefore not practicable since such a combination on the basis of AND or OR operators is only possible after a suitable spatial alignment, dewarping and matching of the scans, which, however, is not disclosed.
In WO 2010/009447 A2, the desired information is contained not only one but in a plurality of display formats. The measurement conditions used for this can even result in different images of the individual regions which are difficult to compare with each other. For example, depending on the position, scans or partial scans can contain angularly and spatially resolved signals. Thus, a scan of the anterior chamber, which scan is telecentric outside of the eye, is inevitably subjected to spatial distortions after the refraction on the cornea, which distortions allow a combination with a scan carried out in a deeper eye plane only after consideration of this refraction.
With the OCT system proposed in WO 2010/009447 A2, merely a solution is proposed with which at best non-dewarped, spatially unmatched A-, B- or C-scans of anterior and posterior eye portions or also individual whole-eye scans of medium or poor signal quality and low, inhomogeneous lateral resolution can be displayed together in a manner unsuitable for diagnostic or biometric purposes.
In particular, no solution is given in order to combine scans of the anterior and posterior eye portions optimized with regard to signal strength and lateral resolution in such a manner that an anatomically correct or true to scale display of the whole eye is implemented, which display is robust with respect to eye movements and is optimized for diagnostic or biometric measures.
Spatial dewarpings of OCT scans on corneas are described, for example, by Drexler and Fujimoto in [2]. Further known are observations of ray paths in eyes having a known geometry as a means for selecting intraocular lenses by means of ray tracing or matrix formalism, as described by Tang et al. in [3].
The necessity to bring the scan rotation point into the pupil/iris plane for measurements behind the pupil is also discussed in more detail by D. Huang et al. in [4]. Thus, vignetting of large angular ranges caused by the pupil during scanning can be largely avoided. In contrast to this, anterior scans are not carried out with a pivot point in the pupil plane so that also the front and back sides of the lens can be spatially resolved. In this connection it was found that retinal OCT scanners are principally suitable for scanning the anterior eye segments, but that the low scanning speed and the typically used near infrared light are disadvantageous. For scanning the anterior transparent eye segments, on the one hand, wavelengths of about 1310 nm prove to be much more effective. On the other hand, in addition to concentric or telecentric scan geometries, sector-shaped scan geometries are also used here.
The OCDR system described in DE 10 2008 051272 A1 serves for the interferometric measurement of eye portion lengths over the entire eye length. A laterally scanning OCDR system is described in which also the focus is variable or switchable in order to implement optimal A-scan signals by means of combination. No solution for the anatomically correct display of combined part-eye or whole-eye OCR scans is proposed. The radiation backscattered from the boundary surfaces of the eye is interferometrically acquired and through time domain-, spectral domain- or Fourier domain-coherence reflectometry, a measurement signal is generated that indicates structures of the eye. With this OCDR system, a solution is made available with which preferably a plurality of high-precision sectional measurements on the eye shall be carried out simultaneously. With the proposed OCDR system, a solution is made available with which eye portion lengths can be measured with high precision over the entire length of the eye. Tomographic OCT recordings of the anterior and posterior eye portions by means of A-, B- or C-scans are not possible with this system.
An OCDR system based on long-coherence-length, tunable lasers (swept-sources) with a scan depth of more than 40 mm in tissue has been proposed in DE 10 2008 063 225 A1. With this system, particularly good signal conditions and low motion sensitivity at all boundary surfaces of the eye can readily be implemented even in the case of very long eyes, as is also shown by an example.
An OCT system based on a swept source with relatively large coherence length and with a depth range of nearly 35 mm is described by Ch. Chong et al. in [5]. With the proposed approach it is principally possible to implement tomographic pictures of the whole eye, on which pictures the contours of cornea, iris, lens and retina are visible to some degree.
However, in the case of an experimental implementation, details of the segments exhibit poor visibility because the implemented lateral resolutions and the signal strengths are rather low. Because of the significant signal drop due to the insufficient coherence length of the source of only 28 mm, only pig eyes with a geometrical length of ca. 20 mm could be measured. For human eyes with a geometrical length of up to 40 mm, this system is insufficient.
As described in the prior art, for OCT scans in the whole eye region it is necessary to position the measuring beam focus in the eye portion to be scanned. The size of the focus is important for the resolution as well as for the signal strength of the measurement signal. Thus, for anterior measurement, the focus should lie in the anterior eye region or even in front of the eye, and for posterior measurements, it should lie in the posterior eye region. In this context, on the one hand, different device-related measurement conditions such as focusing, reference plane (zero delay) and scanning can result in different images of the individual regions, inclusive distortions and different magnification factors. On the other hand, this can also be a result of patient-related different fixation, accommodation or movement.
Furthermore, eye structures can exhibit different double refraction which can result in differences in terms of the polarization characteristics of the light backscattered from the individual structures, and thus can result in signal conditions in the scans which are dependent on the polarization settings.
Furthermore, Reinstein et al. describe in [6] and [7] depth-resolved eye scans by means of which regions in the eye can be displayed which cannot be displayed by means of OCT. Known in the prior art are, for example, high-resolution ultrasound displays of anterior regions of the eye including the peripheral regions of the eye lens behind the iris, or the position of IOLs including the haptics behind the iris. A registered combination of ultrasound data or other tomographic data with OCT data is not described, but would be of interest for several medical-diagnostic applications (inter alia, biometry).
Besides the registrations of OCT scans among each other, there is also the possibility of spatial referencing and correction by means of reference information from other, non-depth-resolving measurement systems, for example, with height information from topographs, as described by Tang et al. in [3]. Besides sectional measurements, topographies or kerarometries are necessary parameters for matching refractive intraocular implants such as IOLs.